Latinos are underrepresented in clinical trials, where they encounter challenges in participation and a lack of effective recruitment and retention strategies. For Latino migrants with mental health and substance use problems, these challenges are even greater. Analyzing results from a multicenter randomized clinical trial for Latino migrants with mental health and substance use problems in Boston, Massachusetts, USA as well as Madrid and Barcelona, Spain, we describe six retention strategies used to facilitate participant engagement in follow-up assessments, and report the sociodemographic, clinical, and educational factors associated with research assessment completion. Among 341 randomized participants, 77% completed the 12-month follow-up and 75% completed at least 3 of the 4 follow-up assessments. Having a high school diploma, being recruited at community centers versus other sites, and having a less severe mental health condition were significantly associated with completing more follow-up interviews. Rigorous and customized methods reflecting participant’s individual context can bolster research assessment completion for diverse Latino populations with behavioral health concerns.